title: Ontogeny of pulmonary alveolar epithelial markers of differentiation.
abstract: We studied differentiation of the pulmonary epithelium in the periphery of fetal rat lung in vivo and in vitro by comparing the ontogeny of cell-surface glycoconjugates with that of surfactant phospholipids. Apical surface binding of the lectin Maclura pomifera agglutinin (MPA) and expression of a 200-kDa MPA-binding glycoprotein (MPA-gp200) was evident at 20 days gestation in type 2 cells, but did not correlate with ultrastructural features of type 2 cell differentiation. Epithelial cells isolated from peripheral lung of 18-day gestation fetal rats displayed hormone-sensitive surfactant synthesis prior to the hormone-insensitive expression of MPA-gp200. Expression of MPA-gp200 occurred in association with the appearance of many new apical surface proteins suggesting a hormone-independent process of polar membrane differentiation. Thus membrane and secretory differentiation are discordant and can be dissociated. In vivo binding of Ricinus communis 1 agglutinin (RCA1), an apical marker of the differentiated alveolar type 1 cell occurred in undifferentiated peripheral lung epithelial cells as early as 18 days gestation, disappeared from differentiating type 2 cells and appeared in differentiated type 1 cells. Both undifferentiated fetal epithelial cells at 18 days gestation and fully differentiated type 1 cells express multiple glycoproteins with terminal beta-linked galactose residues which bind RCA1. Some of these RCA1-binding glycoproteins appear to be similar. These observations suggest that alveolar epithelial type 1 cells may derive directly from undifferentiated peripheral lung epithelial cells as well as from fully differentiated type 2 cells. In addition, terminal differentiation of fetal lung peripheral epithelium into type 1 and type 2 cells may involve repression as well as induction of differentiation-related genes.
authors.affiliation: Pulmonary Center, Boston University School of Medicine, Massachusetts 02118.
authors.forename: M F
authors.initials: MF
authors.lastname: Joyce-Brady
authors.forename: J S
authors.initials: JS
authors.lastname: Brody
mesh_terms: D000375:Aging; D000818:Animals; D000831:Animals, Newborn; D002454:Cell Differentiation; D002462:Cell Membrane / Q000032:analysis / Q000648:ultrastructure; D002478:Cells, Cultured; D005314:Embryonic and Fetal Development; D004847:Epithelial Cells; D004848:Epithelium / Q000502:physiology / Q000648:ultrastructure; D005260:Female; D037102:Lectins; D008562:Membrane Glycoproteins / Q000032:analysis; D008854:Microscopy, Electron; D011247:Pregnancy; D011650:Pulmonary Alveoli / Q000166:cytology / Q000196:embryology* / Q000254:growth & development; D051381:Rats; D011919:Rats, Inbred Strains
chemical_list: D037102:Lectins; D008562:Membrane Glycoproteins